421 ANALYSIS OF SEX HORMONE GENES REVEALS GENDER DIFFERENCES IN THE GENETIC ETIOLOGY OF BLOOD PRESSURE SALT-SENSITIVITY

Abstract

Objective: To examine the association between 799 SNPs in 44 sex hormone genes and BP responses to a dietary-sodium intervention. Methods: A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding-study (307.8 mmol sodium/day) was conducted among 1,906 Han Chinese participants. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. Results: Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453 and rs9383951. For example, men with genotypes C/C, C/T, and T/T of rs9397453 had respective mean DBP responses (95% CI) of: −2.67 (−3.13, −2.22), −1.23 (−1.98, −0.48), and 0.08 (−2.31, 2.47) mmHg to low-sodium intervention (p = 1 × 10−4; false discovery rate (FDR)-q = 0.04); and 1.46 (1.03, 1.89), 0.19 (−0.54, 0.91), and −1.10 (−2.82, 0.61) mmHg to high-sodium intervention (p = 2 × 10−4; FDR-q = 0.04). Mean SBP responses (95% CI) were: −5.70 (−6.19, −5.20), −4.34 (−5.37, −3.31), and −2.65 (−5.15, −0.16) mmHg, respectively, for low-sodium intervention (p = 2 × 10−3; FDR-q = 0.17); and 4.56 (4.12, 4.99), 3.47 (2.63, 4.30), and 1.97 (−0.49, 4.43) mmHg, respectively, for high-sodium intervention (p = 3 × 10−3; FDR-q = 0.40). There were no significant associations between any of the sex hormone gene variants and salt-sensitivity in women, with highly significant genotype-gender interactions noted for ESR1 markers rs9340844, rs9397453, and rs9383951. Conclusions: We identified strong, consistent associations between genetic variants in the ESR1 gene and salt-sensitivity in men. Although replication evidence is needed, our results support a gender-specific role for ESR1 in the etiology of this complex trait.